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Kobe J. Med. Sci.,

Vol. 53, No. 6, pp. 327-333,


Lack of Association between the Dopamine Transporter Gene 3’VNTR Polymorphism and Attention Deficit Hyperactivity Disorder in Chinese Han Children: Case-control and Family-based Studies

Y A P I N G W A N G 1 , Z H A O H U I W A N G 1 , K A I N A N Y A O 1 , K I W A M U T A N A K A 2 , Y U F E N G Y A N G 1 , O S A M U S H I R A K A W A 2 , and KIYOSHI MAEDA 2

1Department of Psychiatry and Psychology, Second Affiliated Hospital, Xi’an Jiaotong University, Xi Wu Lu, Xi’an 710004, China; 2Department of Psychiatry and Neurology, Kobe University Graduate School of Medicine

Received 22 January 2007 /Accepted 1 May 2007

Key words: attention deficit hyperactivity disorder (ADHD), dopamine transporter (DAT1), haplotype-based haplotype relative risk (HHRR) analysis, polymorphism, transmission disequilibrium test (TDT).

Attention deficit hyperactivity disorder (ADHD) is the most common childhood onset neurodevelopment disorder. The etiology is unclear, but is suspected to involve the dopamine system. In this study we used the haplotype-based haplotype relative risk (HHRR) analysis and the transmission disequilibrium test (TDT) to investigate the potential contribution of dopamine transporter (DAT1) gene variants to ADHD. DAT1 gene polymorphisms were assessed in 54 ADHD Chinese Han children and all 108 of their parents and 66 normal child controls. No differences were found in either genotype or allele distributions. The HHRR analysis of the DAT1 polymorphisms suggests that the transmission of this polymorphism is not significantly associated with ADHD. And the TDT result showed that ADHD was not in linkage with the DAT1 gene. These findings do not support the hypothesis that DAT1 gene variants contribute to the pathogenesis of ADHD in Chinese Han population.

Attention deficit hyperactivity disorder (ADHD) is one of the most common, neurodevelopment disorders with childhood onset. Children with ADHD have impairment in their daily routine, family and peer relationships, and academic performance [1-3], so they often have a severe effect on their families and society. The etiology of ADHD is unknown. Therefore understanding the etiology and pathogenesis of ADHD is a key and important challenge in psychiatry. A number of recent studies, including family, twin and adoption studies, have provided various lines of evidences that genetic factors play a substantial role in the etiology of ADHD [4-6].

Methylphenidate is the most frequently prescribed medicine in the treatment of ADHD [7-9] because of its ability to improve ADHD core symptoms as well as associated features including aggression, social interaction, and academic productivity. Methylphenidate is assumed to increase the concentration of dopamine in the synaptic cleft by blocking the dopamine transporter (DAT1)[10], a solute carrier protein that is responsible for the reuptake of dopamine into the presynaptic neuron [11]. Recently, animal studies with DAT1 gene

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